This application is a request to transfer the remaining 18 months of grant support from SUNY Stony Brook to Harvard Medical School. The research described in the original proposal is well underway and the move to Harvard poses only minimal delays in the completion and extension of this research. Originally, I had proposed to study two aspects of sodium channels in excitable membranes, molecular structural parameters and biosynthesis and assembly. Portions of both aspects are completed. We have examined equilibrium competition between metal and organic cations and radiolabeled saxitoxin (STX), and have also studied the potencies of four saxitoxin derivatives, using binding assays and electophysiological methods. The isotopic effects from solvent replacement (D2O) on STX and tetrodotoxin (TTX) have been completely characterized. A study of the appearance of STX receptors during axonal growth has been completed. Currently we are investigating the kinetics of appearance of pharmacologically induced sodium flux and STX binding in developing muscle cells in culture. In the remaining 18 months of the grant we will complete the work on the development of excitability in muscle cells, extend our studies of cation-toxin competition to measure the kinetic parameters of these effects, and analyze the kinetics of channel block by the various STX-derivatives, under voltage-clamp. We will also continue our new work on the isolation and purification of scorpion toxins which is detailed in the progress report.